MS/MS analysis (tandem analysis), which is a type of mass spectrometric technique, is a useful technique for identifying compounds having high molecular weights or analyzing their chemical structures. In recent years, the technique has been widely used in various areas. A commonly known type of mass spectrometer for MS/MS analysis is a triple quadrupole mass spectrometer including a collision cell for performing collision induced dissociation (CID) sandwiched between mass filters located on the front and rear sides of the cell. A so-called “Q-TOF” mass spectrometer, which includes a time-of-flight mass analyzer in place of the rear mass filter in the triple quadrupole mass spectrometer, is structurally more complex and expensive than the triple quadrupole mass spectrometer, but has the advantage that it can acquire more accurate mass spectra. A TOF/TOF type of device in which the front quadrupole mass filter is also replaced by a time-of-flight mass analyzer has also been known.
In the present description, any type of mass spectrometer which can perform an MS/MS analysis by having a configuration including an ion-dissociating section for dissociating ions (which is not limited to a collision cell) sandwiched between front and rear mass analyzers is generally called a tandem mass spectrometer. The tandem mass spectrometer may hereinafter be simply referred to as a mass spectrometer.
Mass spectrometers, which are not limited to tandem mass spectrometers, are often used in combination with liquid chromatographs (LC) or gas chromatographs (GC). In particular, a liquid chromatograph mass spectrometer (LC-MS) or gas chromatograph mass spectrometer (GC-MS), which includes a tandem mass spectrometer combined with a liquid chromatograph or gas chromatograph, is useful for simultaneous multicomponent analysis in which a large number of compounds contained in a sample are simultaneously analyzed. These types of devices are hereinafter collectively called the “chromatograph mass spectrometer”.
When an MS/MS spectrum for a specific component in a sample is to be acquired with a chromatograph mass spectrometer, it is normally necessary to previously set, as one of the analyzing conditions, the mass-to-charge ratio m/z of a precursor ion originating that specific component as the target. Understandably, in the case of acquiring information concerning an unknown component contained in a sample, it is impossible to previously set the mass-to-charge ratio of the precursor ion as one of the analyzing conditions.
A data-acquisition technique for solving the previously described problem in the MS/MS analysis is disclosed in Patent Literature 1. This technique is hereinafter schematically described using FIGS. 4A, 4B, 5A and 5B.
In a mass spectrometer, a normal mass spectrometric analysis which includes no ion-dissociating operation is repeatedly performed at predetermined intervals of time. FIG. 4A is a mass spectrum obtained by one mass spectrometric analysis. Within the period of time from the completion of one execution of a mass spectrometric analysis to the next execution of the same mass spectrometric analysis, an MS/MS analysis is performed for each of the mass-to-charge-ratio sections defined by dividing the entire mass-to-charge-ratio range by a predetermined mass-to-charge-ratio width ΔM, as shown in FIG. 4B. In the example of FIG. 4B, since the entire mass-to-charge-ratio range is divided into ten sections, the MS/MS analysis is performed ten times for each execution of the normal mass spectrometric That is to say, one normal mass spectrometric analysis and ten subsequent MS/MS analyses constitute one measurement cycle. Through the repetition of this measurement cycle, mass spectrum data and MS/MS spectrum data are accumulated. For example, in the method described in Patent Literature 1, the mass-to-charge-ratio width ΔM mentioned earlier is set to be equal to or greater than 15 amu. The width ΔM can be appropriately determined according to the breadth of the entire mass-to-charge-ratio range to be covered by the measurement as well as the width with which the precursor ion can be accurately filtered at the stage prior to the CID.
As can be understood from FIGS. 4A and 4B, the number of ion species included within the mass-to-charge-ratio width ΔM can vary with the section; there may be one kind of ion or multiple kinds of ions, or in some cases, there may be no ion included within the mass-to-charge-ratio width ΔM. Regardless of such a variation, the MS/MS analysis is always performed in such a manner that all ion species included within the mass-to-charge-ratio width ΔM are collectively designated as precursor ions. FIG. 5A shows one example of the MS/MS spectrum. If ion species originating from different components are collectively designated as precursor ions in the MS/MS analysis, the product ions originating from those different components will appear in a mixed form on the MS/MS spectrum. On such an MS/MS spectrum, it is almost impossible to determine, for each product ion, which component is the origin of that product ion.
After the completion of the measurement, the mass spectra and MS/MS spectra sequentially obtained with the passage of time are analyzed to identify the compounds contained in the sample. For example, in the method described in Patent Literature 1, an extracted ion chromatogram (which is conventionally called the “mass chromatogram”) corresponding to the mass-to-charge ratio of a peak in an MS/MS spectrum of each compound is created from the measurement data, based on a collection of MS/MS spectra (spectrum library) previously obtained for known compounds. Whether or not the compound is present is determined with reference to an index which shows the degree of matching of the created extracted ion chromatogram with a pattern which is predicted from the spectrum library.
On the other hand, in a method described in Patent Literature 2, peaks (mass peaks) are detected from the mass spectra and MS/MS spectra sequentially obtained with the passage of time, and an extracted ion chromatogram is created for each of the mass-to-charge ratios of those peaks. The precursor ion and product ions originating from the same component have their respective peaks (chromatogram peaks) at the same retention time on the extracted ion chromatograms. Accordingly, as shown in FIG. 5B, the precursor ion and product ions located at the same retention time are collected, and the mass information of those ions are compared with a compound database to identify the precursor ion, i.e. the original component. In the example of FIGS. 5A and 5B, the original component is identified from the precursor ion and three product ions (m/z=M1, M2 and M3) having the same retention time t1.
In any of the previously described techniques, an exhaustive MS/MS analysis for various kinds of ion peaks observed on a mass spectrum is preformed, rather than an MS/MS analysis in which a specific ion peak observed on a mass spectrum is designated as the target. Therefore, various components contained in a sample can be almost completely identified. Those techniques also allow for a quantitative analysis based on the area of a peak in an extracted ion chromatogram.
In the previously described techniques, the retention time of the peak on the created extracted ion chromatogram (chromatogram peak) is an important index for identifying the precursor ion. Accordingly, in order to improve the accuracy of the identification of the precursor ion, it is necessary to improve the correctness of the retention time of the chromatogram peak. To this end, it is necessary to increase the number of data points forming the peak on the extracted chromatogram. Increasing the number of data points forming a peak is also essential for improving the accuracy of the peak shape in a quantitative analysis based on the area of a peak on an extracted ion chromatogram.
The number of data points per unit time decreases with an increase in the length of time of one measurement cycle. Therefore, for example, if the mass-to-charge-ratio width ΔM is constantly maintained, increasing the number of times of the execution of the MS/MS analysis to widen the entire mass-to-charge-ratio range to be covered by the measurement will decrease the number of data points per unit time. Similarly, setting a narrower mass-to-charge-ratio width ΔM to decrease the number of target components in one MS/MS analysis will also increase the number of times of the execution of the MS/MS analysis and consequently decrease the number of data points per unit time.
As one technique for increasing the number of data points per unit time, for example, if the rear mass analyzer is a quadrupole mass filter, the control sequence may be modified so as to increase the scan rate of the voltages applied to the electrodes forming the filter and thereby shorten the time required for one execution of the MS/MS analysis. If the rear mass analyzer is a time-of-flight mass analyzer, the control sequence may be modified so as to increase the amount of acceleration energy for ejecting ions into the flight space and thereby shorten the time required for one execution of the MS/MS analysis. However, those methods may possibly lower the sensitivity or reproducibility of the MS/MS spectrum to be eventually obtained. It is therefore difficult to create an extracted ion chromatogram with a high level of quality.